Natural Killer Cells In Tissues Research Articles

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expressed by in vitro activated natural killer (NK) cells, but the relevance of this observation to the biological function of NK cells has been unclear. Herein, we have demonstrated the in vivo induction of mouse TRAIL expression on various tissue NK cells and correlated NK cell activation with TRAIL-mediated antimetastatic function in vivo. Expression of TRAIL was only constitutive on a subset of liver NK cells, and innate NK cell control of Renca carcinoma hepatic metastases in the liver was partially TRAIL dependent. Administration of therapeutic doses of interleukin (IL)-12, a powerful inducer of interferon (IFN)-gamma production by NK cells and NKT cells, upregulated TRAIL expression on liver, spleen, and lung NK cells, and IL-12 suppressed metastases in both liver and lung in a TRAIL-dependent fashion. By contrast, alpha-galactosylceramide (alpha-GalCer), a powerful inducer of NKT cell IFN-gamma and IL-4 secretion, suppressed both liver and lung metastases but only stimulated NK cell TRAIL-mediated function in the liver. TRAIL expression was not detected on NK cells from IFN-gamma-deficient mice and TRAIL-mediated antimetastatic effects of IL-12 and alpha-GalCer were strictly IFN-gamma dependent. These results indicated that TRAIL induction on NK cells plays a critical role in IFN-gamma-mediated antimetastatic effects of IL-12 and alpha-GalCer.

Characterization of murine decidual natural killer (NK) cells and their relevance to the success of pregnancy

The identification of lytic cells in 6.5-day to 9.5-day murine decidua as NK cells has been extended. The cells with natural killer (NK) activity in early decidua were nonphagocytic and heterogeneous in size as assessed by velocity sedimentation at unit gravity. The numbers of lytic cells were reduced by treatment with anti-asialo GM1 in vivo and they were absent from the decidua of bg/bg mice. Thus, decidual NK cells were not distinct from NK cells in other tissues. The decline in the levels of decidual NK activity as pregnancy progressed was attributed to their regulation by other cells present in decidua by midgestation. The development of NK activity in decidua was dependent upon the presence of an embryo, however, decidual NK cells were not essential for successful pregnancy because viable offspring were obtained from mice lacking decidual NK activity. It was shown that NK cells from either spleen or decidua were unlikely to cause damage to embryos during the first half of pregnancy as freshly dissociated 9.5- and 11.5-day embryonic cells resisted NK lysis. Furthermore, blastocysts were not damaged by coincubation with splenic or decidual NK cells and were viable upon subsequent embryo transfer. These studies indicate that decidual NK cells are not essential for successful pregnancy and are not necessarily detrimental to early embryos. It is suggested that decidual NK cells may play other nonimmunological roles during embryonic development.

Natural killer-like cells found in B-cell compartments of human lymphoid tissues.

Natural killer (NK) cells have been implicated in natural resistance to tumours, particularly lymphomas. Recently, they have been implicated in the regulation of human erythropoiesis. The distribution of NK cells in peripheral lymphoid tissues has not been fully documented. NK activity in human or murine lymph nodes is significantly lower than in the spleen or peripheral blood. In Hodgkin's disease, affected lymph nodes and spleens have higher NK activity than non-involved nodes or spleens. Using a monoclonal antibody (Leu 7) that defines the human NK antigen HNK-1 (ref. 8), only a small number of HNK-1+ cells were found in lymph nodes, tonsils or thymus, with greater numbers in the spleen. We report here the topographical distribution of HNK-1+ cells in normal human lymph nodes, tonsils and spleen and preliminary observations in various forms of malignant lymphoma. The most striking observation was that HNK-1+ cells were not distributed uniformly in these tissues but specifically localized in the B-cell compartments (follicular centres).

Tissue distribution of human NK cells studied with anti-Leu-7 monoclonal antibody.

The distribution and numbers of human natural killer (NK) cells in different lymphoid tissues and several tumors were determined with the use of monoclonal antibody to the Leu-7 antigen and immunohistologic methods. Anti-Leu-7 reacts with large granular lymphocytes containing most of NK activity in the peripheral blood. The Leu-7+ cells were found mainly in the germinal centers of secondary follicles in lymph nodes, spleens, and tonsils. The mean number of Leu-7+ cells in 40 germinal centers was 223 +/- 103 SD. Only rare cells were found in the thymus. In the follicles studied in serial sections, the distribution of the Leu-7+ cells was distinctly different from that of T cells, B cells and Ia+ cells. The Leu-7+ cells did not react with OKT 6 antibody specific for immature (control) thymocytes and Langerhans' cells. By double staining techniques, two populations of Leu-7+ cells were identified in lymphoid tissues: those that did and did not express the Ia-like antigen. The numbers and localization of the Leu-7+ cells varied in different tumors, but often the Leu-7+ cells surrounded the neoplastic nodules or were seen in contact with individual cancer cells. Anti-Leu-7 may be a useful reagent for monitoring the presence and localization of NK cells in normal and malignant human tissues.